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1.
Artigo em Inglês | MEDLINE | ID: mdl-38655853

RESUMO

BACKGROUND AND AIM: Depression is highly prevalent in patients with inflammatory bowel disease (IBD), which may affect the prognosis of IBD. This aimed to investigate the impact of depression on prognosis in IBD. METHODS: A systematic literature search was performed in four databases (Medline, Embase, Web of Science, and PsycINFO) up to December 31, 2023. Studies were included if they investigated the impact of depression on prognosis in IBD. The primary outcome was flare in IBD, and secondary outcomes were hospitalization, readmission, emergency visits, surgery, and escalation of medical therapy. Relative risks (RRs) were utilized to estimate the risk in each of the above prognostic indicators. RESULTS: Fourteen cohort and 10 case-control studies matched our entry criteria, comprising 630 408 patients with IBD. Twenty-two of included studies were considered to have a low risk of bias. Depression was found to significantly increase the risk of flare (RR = 1.37, 95% CI 1.16-1.63), hospitalization (RR = 1.11, 95% CI 1.00-1.23), readmission (RR = 1.32, 95% CI 1.04-1.67), emergency visits (RR = 1.33, 95% CI 1.12-1.59), surgery (1.38, 95% CI 1.08-1.76), and escalation of medical therapy (RR = 1.38, 95% CI 1.13-1.69) in IBD. Of note, patients with depression in ulcerative colitis had significant differences in readmission (RR = 1.38, 95% CI 1.19-1.60) and escalation of medical therapy (RR = 1.78, 95% CI 1.55-2.04). Additionally, the association was observed in patients with Crohn's disease in terms of flare (RR = 1.47, 95% CI 1.08-2.01) and hospitalization (RR = 1.20, 95% CI 1.03-1.40). CONCLUSIONS: Current evidence suggested that depression could significantly increase the risk of poor prognosis worsening in patients with IBD. However, the association varied in IBD subtypes.

2.
Zhongguo Zhong Yao Za Zhi ; 49(7): 1896-1904, 2024 Apr.
Artigo em Zh | MEDLINE | ID: mdl-38812202

RESUMO

This study aims to analyze the constituents of Jiaotai Pills migrating to the blood in normal rats by UHPLC-TOF-MS technique and reveal the underlying mechanism of Jiaotai Pills in the treatment of depression by network pharmacology and animal experiments. UHPLC-TOF-MS technique was used to detect the constituents of Jiaotai Pills in the blood of rats after intragastric administration. The intersection target of the constituents and depression was screened by DisGeNET and SwissTargetPrediction database, and the protein-protein interaction(PPI) network was constructed. Key targets were imported into the DAVID platform for Gene Ontology(GO) analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway annotation. Combined with constituents, targets, and pathways, the "constituent-target-pathway" network was constructed by Cytoscape 3.9.1 software, through which the key targets and pathways of Jiaotai Pills against depression were predicted. The depression model of chronic unpredictable mild stress(CUMS) was established on rats. After that, behavioral experiments were conducted. The expression of inflammatory factors in serum and the neurotransmitters in the brain were detected by ELISA, and the expression of key targets in the hippocampus was detected by Western blot. The results showed that a total of 17 constituents of Jiaotai Pills were identified in the blood, including 10 alkaloids. There were 124 intersection targets between constituents of Jiaotai Pills and depression disorder. A total of 52 core targets were screened according to PPI results, including NLRP3 and caspase-1, etc. KEGG enrichment analysis mainly involved 15 typical pathways such as NOD-like receptor pathway. The results of animal experiments showed that Jiaotai Pills significantly improved the depression-like behavior of CUMS depressive model on rats, decreased the levels of IL-1ß, TNF-α and IL-6 in serum, and increased the expression of neurotransmitters such as 5-hydroxytryptamine(5-HT), dopamine(DA), and norepinephrine(NE) in the brain. Besides, Jiaotai Pills also down-regulated the expression of NLRP3 and caspase-1 proteins in the hippocampus and inhibited the NLRP3-mediated NOD-like receptor signaling pathway. In conclusion, Jiaotai Pills may play a role in the treatment of depression by inhibiting the NLRP3 inflammasome and the NOD-like receptor pathway mediated by NLRP3.


Assuntos
Depressão , Medicamentos de Ervas Chinesas , Farmacologia em Rede , Ratos Sprague-Dawley , Animais , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacologia , Depressão/tratamento farmacológico , Depressão/genética , Depressão/metabolismo , Ratos , Masculino , Cromatografia Líquida de Alta Pressão , Mapas de Interação de Proteínas , Espectrometria de Massas , Humanos , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo
3.
Anal Chem ; 95(6): 3309-3316, 2023 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-36716054

RESUMO

Photochromic sensors have the advantages of diverse isomers for multi-analysis, providing more sensing information and possessing more recognition units and more sensitivity to external stimulations, but they present enormous complexity with various stimulations as well. Deep learning (DL) algorithms contribute a huge advantage at analyzing nonlinear and multidimensional data, but they suffer from nontransparent inner networks, "black-boxes". In this work, we employed the explainable DL approach to process and explicate photochromic sensing. Spirooxazine metallic complexes were adopted to prepare a multi-state analysis array for ß-Lactams identification and quantitation. A dataset of 2520 unduplicated fluorescence intensity images was collected for convolutional neural network (CNN) operation. The method clearly discriminated six ß-Lactams with 97.98% prediction accuracy and allowed rapid quantification with a concentration range from 1 to 100 mg/L. The photochromic sensing mechanism was verified via molecular simulation and class activation mapping, which explicated how the CNN model assesses the importance of photochromic sensor states and makes a discrimination decision. The explainable DL-assisted analysis method establishes an end-to-end strategy to ascertain and verify the complicated sensing mechanism for device optimization and even new scientific discovery.


Assuntos
Aprendizado Profundo , Redes Neurais de Computação , Algoritmos , beta-Lactamas , Antibacterianos
4.
Small ; 19(39): e2302811, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37194977

RESUMO

Polymerized ionic liquids (PILs) with super ion diffusion kinetics have aroused considerable attention in rechargeable batteries, which are very promising to solve the problem of the slow ion diffusion kinetics in organic electrode materials. Theoretically, PILs incorporated redox groups are very suitable as anode materials to realize "superlithiation" performance, achieving high lithium storage capacity. In this study, redox pyridinium-based PILs (PILs-Py-400) have been synthesized through trimerization reactions by pyridinium ionic liquids with cyano groups under an appropriate temperature (400 °C). The positively charged skeleton, extended conjugated system, abundant micropores, and amorphous structure for PILs-Py-400 can boost the utilization efficiency of redox sites. A high capacity of 1643 mAh g-1 at 0.1 A g-1 (96.7% of the theoretical capacity) has been obtained, indicating intriguing 13 Li+ redox reactions in per repeating unit of one pyridinium ring, one triazine ring, and one methylene. Moreover, PILs-Py-400 exhibit excellent cycling stability with a capacity of around 1100 mAh g-1 at 1.0 A g-1 after 500 cycles, and the capacity retention is 92.2%.

5.
J Org Chem ; 88(13): 8279-8285, 2023 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-37257025

RESUMO

A method for chemoselective reduction of 2-pyridyl ketones and related N-heteroaryl compounds catalyzed by cobalt stearate using DMF as a hydride source is developed. The ketone substrate is activated by chelation with cobalt, which makes the present method highly chemoselective. A possible reaction mechanism is proposed on the basis of control experiments.


Assuntos
Dimetilformamida , Cetonas , Estrutura Molecular , Cetonas/química , Cobalto/química , Catálise
6.
Zhongguo Zhong Yao Za Zhi ; 48(23): 6500-6508, 2023 Dec.
Artigo em Zh | MEDLINE | ID: mdl-38212007

RESUMO

This study aimed to investigate the effect of Jiaotai Pills on protein expression in the hippocampus of the rat model of chronic unpredictable mild stress(CUMS)-induced depression by quantitative proteomics and explore the anti-depression mechanism of Jiaotai Pills. The SD rats were randomized into control, model, Jiaotai Pills, and fluoxetine groups(n=8). Other groups except the control group were subjected to CUMS modeling for 4 weeks. After 4 weeks of continuous administration, the changes of behavior and pathological morphology of the hippocampal tissue were observed. Proteins were extracted from the hippocampal tissue, and bioinformatics analysis was performed for the differentially expressed proteins(DEPs) identified by quantitative proteomics. Western blot was employed to verify the key DEPs. The results showed that Jiaotai Pills significantly alleviated the depression behaviors and hippocampal histopathological changes in the rat model of CUMS-induced depression. A total of 5 412 proteins were identified in the hippocampus of rats, including 65 DEPs between the control group and the model group and 35 DEPs between the Jiaotai Pills group and the model group. There were 16 DEPs with the same trend in the Jiaotai Pills group and the control group, which were mainly involved in sphingolipid, AMPK, and dopaminergic synapse signaling pathways. The Western blot results of Ppp2r2b, Cers1, and Ndufv3 in the hippocampus were consistent with the results of proteomics. In conclusion, Jiaotai Pills may play an anti-depression role by modulating the levels of Ppp2r2b, Cers1, Ndufv3 and other proteins and regulating sphingolipid, AMPK, and dopaminergic synapse signaling pathways.


Assuntos
Proteínas Quinases Ativadas por AMP , Depressão , Medicamentos de Ervas Chinesas , Ratos , Animais , Ratos Sprague-Dawley , Depressão/tratamento farmacológico , Proteínas Quinases Ativadas por AMP/metabolismo , Proteômica , Hipocampo , Estresse Psicológico/metabolismo , Esfingolipídeos/metabolismo , Modelos Animais de Doenças
7.
Zhongguo Zhong Yao Za Zhi ; 48(1): 183-192, 2023 Jan.
Artigo em Zh | MEDLINE | ID: mdl-36725270

RESUMO

This study aims to explore the anti-depression mechanism of Zuojin Pills based on the plasma constituents, network pharmacology, and experimental verification. UHPLC-TOF-MS was used for qualitative analysis of Zuojin Pills-containing serum. Targets of the plasma constituents and the disease were retrieved from PharmMapper and GeneCards. Then the protein-protein interaction(PPI) network was constructed and core targets were screened for GO term enrichment and KEGG pathway enrichment. Cytoscape 3.7.2 was employed construct the "compound-target-pathway" network and the targets and signaling pathways of Zuojin Pills against depression were predicted. CUMS-induced depression mouse model was established to verify the key targets. The results showed that a total of 21 constituents migrating to blood of Zuojin Pills were identified, which were mainly alkaloids. A total of 155 common targets of the constituents and the disease and 67 core targets were screened out. KEGG enrichment and PPI network analysis showed that Zuojin Pills may play a role in the treatment of depression through AMPK/SIRT1, NLRP3, insulin and other targets and pathways. Furthermore, the results of animal experiments showed that Zuojin Pills could significantly improve the depression behaviors of depression, reduce the levels of IL-1ß, IL-6 and TNF-α in hippocampus and serum, activate AMPK/SIRT1 signaling, and reduce the protein expression of NLRP3. In conclusion, Zuojin Pills may play a role in the treatment of depression by activating AMPK/SIRT1 signaling pathway, and inhibiting NLRP3 activation and neuroinflammation in the hippocampus of mice.


Assuntos
Medicamentos de Ervas Chinesas , Farmacologia em Rede , Animais , Camundongos , Proteínas Quinases Ativadas por AMP , Cromatografia Líquida de Alta Pressão , Proteína 3 que Contém Domínio de Pirina da Família NLR , Sirtuína 1 , Medicamentos de Ervas Chinesas/farmacologia , Simulação de Acoplamento Molecular
8.
J Phys Chem A ; 126(38): 6695-6709, 2022 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-36108160

RESUMO

In order to design new Ag(I)-based materials for thermally activated delayed fluorescence (TADF), it is vital to develop a detailed understanding of the current best performing materials. The quantitative predictions of the photophysical processes of the Ag(dmp)(P2-nCB) TADF complex are calculated using time-dependent density functional theory (TD-DFT) combined with the path integral approach for dynamics including the Herzberg-Teller effects. All calculated results are in good agreement with the experimentally available data, demonstrating the validity of our applied theoretical approach. Analysis of ETS-NOCV (extended transition state natural orbital for chemical valence) shows that there is a weak bond interaction dominated by electrostatic interactions and accompanied by some covalent components between Ag(I) and dmp ligands due to the introduction of the strongly electron-donating negatively charged P2-nCB ligand, thus giving a small energy separation between the lowest singlet S1 and triplet T1 states of ΔE(S1 - T1) ≈ 532 cm-1. The SOC strongly depends on the geometrical alteration caused by the molecular "promotion" vibrations. Our study has revealed that a few "promotion" vibrational modes, that is, ω46 and ω227, effectively induce the strong SOC between S1 and T1 and speed up the reverse intersystem crossing (RISC) process dramatically. The computed kRISC value is 1.19 × 107 s-1 for the solid phase at 300 K, which are about 5 orders of magnitude larger than the mean phosphorescence rate, kP = 9.56 × 102 s-1, and it is also far larger than ISC k0ISC = 7.84 × 102 s-1 rates from T1 to S0. The S1 state thus can be an efficient thermal repopulation from the T1 state by the RISC pathway. Finally, we also note that the diabatic vibration coupling triplet pair T1/T2 will also be important for efficient and practical RISC. Our investigation will be of great utility toward designing and improving the Ag(I)-based TADF complexes.

9.
Biomed Chromatogr ; 36(2): e5261, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34716608

RESUMO

A rapid and sensitive LC-MS/MS method was developed and validated for the simultaneous determination of nicotinamide and its metabolite N1 -methylnicotinamide in human serum. Serum samples were prepared by protein precipitation with acetonitrile. The chromatographic separation was performed on a Waters Spherisorb S5 CN microbore column (2.0 × 100 mm, 5 µm) with gradient elution within 7 min. Acetonitrile and 5 mm ammonium formate aqueous solution (containing 0.1% formic acid) were used as mobile phases. Nicotinamide, N1 -methylnicotinamide and N'-methylnicotinamide (internal standard) were detected with a triple-quadrupole tandem mass spectrometer in the positive ion mode. Multiple reaction monitoring was used to monitor precursor to product ion transitions of m/z 123.1 → 80.1 for nicotinamide, m/z 137.1 → 94.1 for N1 -methylnicotinamide and m/z 137.1 → 80.1 for the internal standard. The linear ranges of nicotinamide and N1 -methylnicotinamide were 5.000-160.0 and 2.500-80.00 ng/ml, respectively. The intra- and inter-day precisions (RSD) of both analytes were within 6.90%. The recoveries were >88%. The analytes were proven to be stable during all sample storage, preparation and analytic procedures. The method was successfully applied to determine the concentrations of nicotinamide and N1 -methylnicotinamide in human serum to investigate the association between their concentrations and obesity in 1160 Chinese subjects.


Assuntos
Cromatografia Líquida/métodos , Niacinamida/análogos & derivados , Niacinamida/sangue , Obesidade/sangue , Espectrometria de Massas em Tandem/métodos , Adulto , Humanos , Limite de Detecção , Modelos Lineares , Pessoa de Meia-Idade , Reprodutibilidade dos Testes
10.
Zhongguo Zhong Yao Za Zhi ; 47(18): 5079-5087, 2022 Sep.
Artigo em Zh | MEDLINE | ID: mdl-36164918

RESUMO

A high-performance liquid chromatography-tandem mass spectrometry(LC-MS/MS) was developed for simultaneously determining the components(magnoflorine, jatrorrhizine, berberrubine, coptisine, berberine) of Jiaotai Pills and Fluoxetine in plasma of rats with chronic unpredictable mild stress(CUMS)-induced depression to investigate the pharmacokinetic herb-drug interaction of Jiaotai Pills and Fluoxetine in the rats. The six components showed good linear relationship within the corresponding concentration ranges, and the method showed high specificity, accuracy, precision, and stability. Their pharmacokinetic parameters were calculated by DAS 3.2.2, and the results showed that the in vivo metabolic processes of the six components accorded with the characteristics of non-compartmental model. When Jiaotai Pills and Fluoxetine were used together, the AUC_(0-t), AUC_(0-∞), C_(max), and C_(av) of magnoflorine all significantly increased(P<0.05), while the pharmacokinetic trend of berberrubine was opposite to that of magnoflorine, as manifested by the decrease in AUC_(0-t), AUC_(0-∞), T_(max), C_(max), and C_(av)(P<0.01, P<0.05). The pharmacokinetic characteristics of jatrorrhizine, coptisine, and berberine followed the trend of berberrubine. There was no significant difference in the pharmacokinetic characteristics of Fluoxetine in the single or combination groups. This study suggests that the enhanced antidepressant efficacy of Jiaotai Pills and Fluo-xetine may be attributed to the pharmacokinetic interaction.


Assuntos
Berberina , Fluoxetina , Animais , Cromatografia Líquida/métodos , Depressão/tratamento farmacológico , Medicamentos de Ervas Chinesas , Ratos , Espectrometria de Massas em Tandem/métodos
11.
Small ; 17(32): e2101727, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34216433

RESUMO

Transition metal oxides (TMOs) have been under the spotlight as promising precatalysts for electrochemical oxygen evolution reaction (OER) in alkaline media. However, the slow and incomplete self-reconstruction from TMOs to (oxy)hydroxides as well as the formed (oxy)hydroxides with unmodified electronic structure gives rise to the inferior OER performance to the noble metal oxide ones. Herein, a unique dual metal oxides lattice coupling strategy is proposed to fabricate carbon cloth-supported ultrathin nanowires arrays, which are composed of pseudo-periodically welded NiO with CeO2 nanocrystals (NiO/CeO2 NW@CC). When served as an OER precatalyst in 1.0 m KOH, the NiO/CeO2 NW@CC shows an ultralow overpotential of 330 mV at 50 mA cm-2 , along with an impressive cycle durability of more than 3 days even at 50 mA cm-2 , surpassing CC-supported NiO and commercial IrO2 catalysts. The combined experimental and theoretical investigations unveil that the atomic coupling of CeO2 can not only appreciably trigger the generation of oxygen vacancies and expedite phase transformation of NiO into active NiOOH, but also in situ create a chemical bond with the formed NiOOH and enable the electron injection, thus effectively inhibiting the aggregation of the accessible NiOOH nanodomains and optimizing their reaction free energy towards oxygen-containing intermediates.

12.
Acta Pharmacol Sin ; 42(2): 230-241, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32770173

RESUMO

Sirtuin 3 (SIRT3) is a potential therapeutic target for cardiovascular, metabolic, and other aging-related diseases. In this study, we investigated the role of SIRT3 in diabetic cardiomyopathy (DCM). Mice were injected with streptozotocin (STZ, 60 mg/kg, ip) to induce diabetes mellitus. Our proteomics analysis revealed that SIRT3 expression in the myocardium of diabetic mice was lower than that of control mice, as subsequently confirmed by real-time PCR and Western blotting. To explore the role of SIRT3 in DCM, SIRT3-knockout mice and 129S1/SvImJ wild-type mice were injected with STZ. We found that diabetic mice with SIRT3 deficiency exhibited aggravated cardiac dysfunction, increased lactate dehydrogenase (LDH) level in the serum, decreased adenosine triphosphate (ATP) level in the myocardium, exacerbated myocardial injury, and promoted myocardial reactive oxygen species (ROS) accumulation. Neonatal rat cardiomyocytes were transfected with SIRT3 siRNA, then exposed to high glucose (HG, 25.5 mM). We found that downregulation of SIRT3 further increased LDH release, decreased ATP level, suppressed the mitochondrial membrane potential, and elevated oxidative stress in HG-treated cardiomyocytes. SIRT3 deficiency further raised expression of necroptosis-related proteins including receptor-interacting protein kinase 1 (RIPK1), RIPK3, and cleaved caspase 3, and upregulated the expression of inflammation-related proteins including NLR family pyrin domain-containing protein 3 (NLRP3), caspase 1 p20, and interleukin-1ß both in vitro and in vivo. Collectively, SIRT3 deficiency aggravated hyperglycemia-induced mitochondrial damage, increased ROS accumulation, promoted necroptosis, possibly activated the NLRP3 inflammasome, and ultimately exacerbated DCM in the mice. These results suggest that SIRT3 can be a molecular intervention target for the prevention and treatment of DCM.


Assuntos
Diabetes Mellitus Experimental/complicações , Cardiomiopatias Diabéticas/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Sirtuína 3/genética , Animais , Diabetes Mellitus Experimental/genética , Inflamassomos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Miocárdio/patologia , Miócitos Cardíacos/patologia , Necroptose/genética , Estresse Oxidativo/genética , Ratos , Ratos Sprague-Dawley , Estreptozocina
13.
J Sep Sci ; 44(14): 2754-2763, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34008891

RESUMO

Epoxide hydrolases catalyze the hydrolysis of both exogenous and endogenous epoxides to the corresponding vicinal diols by adding water. Microsomal and soluble epoxide hydrolase are two main mammalian enzymes that have been intensely characterized. The purpose of this investigation was to develop and validate a proteomics assay allowing the simultaneous quantification of microsomal and soluble epoxide hydrolase in rats. Protein quantification was realized through targeted proteomics using liquid chromatography with tandem mass spectrometry for the determination of trypsin-specific surrogate peptides after digestion. Stable isotope-labeled peptides were used as the internal standards. The chromatography of the surrogate peptides was performed on an Agilent SB C18 column (100 mm × 4.6 mm, 1.8 µm) with gradient elution. Acetonitrile containing 0.1% formic acid and 0.1% formic acid aqueous solution were used as mobile phases. A multiple reaction monitoring method in a positive ionization mode was used for the simultaneous detection of the peptides. The method was validated concerning the specificity, linearity, within-day and between-day accuracy and precision, matrix effect, stability, and digestion efficiency. The developed assay was successfully used to quantify the protein levels of microsomal and soluble epoxide hydrolase in rat liver, kidney, and heart S9 samples.


Assuntos
Epóxido Hidrolases/análise , Proteômica/métodos , Espectrometria de Massas em Tandem/métodos , Animais , Cromatografia Líquida/métodos , Marcação por Isótopo , Rim/química , Fígado/química , Espectrometria de Massas/métodos , Miocárdio/química , Peptídeos/análise , Ratos , Espectrometria de Massas por Ionização por Electrospray/métodos
14.
Zhongguo Zhong Yao Za Zhi ; 46(14): 3687-3693, 2021 Jul.
Artigo em Zh | MEDLINE | ID: mdl-34402293

RESUMO

A LC-MS/MS method was developed for the rapid and simultaneous determination of genipin-1-ß-D-gentiobioside,geniposide,naringin,hesperidin and neohesperidin in SD rat plasma.The linear relationships of these five constituents in rats were validated,and the specificity,accuracy,precision and stability met the requirements.Their pharmacokinetic parameters were calculated by DAS 3.2.2,and the results showed that the metabolic process in vivo of the five constituents accorded with the characteristics of noncompartmental model.Their main pharmacokinetic parameters were listed as follows:(1) genipin-1-ß-D-gentiobioside:t_(1/2)(3.20±0.51)h,C_(max)(403.15±96.93)µg·L~(-1)and AUC_(0-t)(612.56±148.50)µg·L~(-1)·h for the model group,while t_(1/2)(3.07±0.75) h,C_(max)(229.50±60.63)µg·L~(-1)and AUC_(0-t)(413.14±76.37)µg·L~(-1)·h for the normal group;(2) geniposide:t_(1/2)(3.24±0.68) h,C_(max)(2 961.40±688.02)µg·L~(-1),and AUC_(0-t)(10 972.87±1 992.96)µg·L~(-1)·h for the model group,while t_(1/2)(4.56±0.96) h,C_(max)(1 833.27±558.13)µg·L~(-1),and AUC_(0-t)(8 996.27±3 053.48)µg·L~(-1)·h for the normal group;(3) naringin:t_(1/2)(1.64±0.59) h,C_(max)(415.13±259.54)µg·L~(-1),and AUC_(0-t)(608.62±289.05)µg·L~(-1)·h for the model group,while t_(1/2)(1.02±0.25) h,C_(max)(355.08±180.00)µg·L~(-1),and AUC_(0-t)(501.07±242.68)µg·L~(-1)·h for the normal group;(4) hesperidin:t_(1/2)(0.86±0.29) h,C_(max)(95.17±22.80)µg·L~(-1)and AUC_(0-t)(141.19±54.63)µg·L~(-1)·h for the model group,while t_(1/2)(0.95±0.31) h,C_(max)(46.48±18.33)µg·L~(-1)and AUC_(0-t)(69.51±14.73)µg·L~(-1)·h for the normal group;(5) neohesperidin:t_(1/2)(0.89±0.29) h,C_(max)(828.78±361.56)µg·L~(-1)and AUC_(0-t)(1 292.29±553.73)µg·L~(-1)·h for the model group,while t_(1/2)(0.90±0.31) h,C_(max)(314.68±172.45)µg·L~(-1)and AUC_(0-t)(385.99±138.55)µg·L~(-1)·h for the normal group.


Assuntos
Medicamentos de Ervas Chinesas , Espectrometria de Massas em Tandem , Animais , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Ratos , Ratos Sprague-Dawley
15.
Zhongguo Zhong Yao Za Zhi ; 46(24): 6511-6519, 2021 Dec.
Artigo em Zh | MEDLINE | ID: mdl-34994144

RESUMO

The present study investigated the effects and mechanisms of Jiaotai Pills on depressed mice induced by chronic unpredictable mild stress(CUMS). The CUMS-induced depression model mice were established and the depression behaviors of mice were evaluated by sucrose preference test, open field test, tail suspension test, and forced swimming test. Molecular docking was employed to simulate the interaction of six main active ingredients in Jiaotai Pills with SIRT1. Immunohistochemical staining was used to detect the level of SIRT1 in the hippocampus of mice. Western blot was used to detect the protein expression levels of SIRT1, p-NF-κB p65, NF-κB p65, and FoxO1 in the hippocampus of mice. Enzyme-linked immunosorbent assay(ELISA) kits were used to detect the levels of interleukin(IL)-1ß, IL-6, tumor necrosis factor-α(TNF-α), and brain-derived neurotrophic factor(BDNF) in the hippocampus and serum of mice. Biochemical kits were used to detect superoxide dismutase(SOD) activity and malondialdehyde(MDA) and glutathione(GSH) levels in the hippocampus and serum of mice. Liquid chromatography-tandem mass spectrometry(LC-MS/MS) was used to detect the levels of dopamine(DA), 5-hydroxytryptamine(5-HT), and norepinephrine(NE) in the hippocampus and serum of mice. The results showed that the sucrose preference rate, movement distance, and the number of crossing centers were reduced in the model group(P<0.01), and the tail suspension time and swimming immobility time were increased(P<0.01). Molecular docking results indicated good binding of six main active ingredients in Jiaotai Pills to SIRT1. In the hippocampus, the expression level of SIRT1 was reduced(P<0.01), and the levels of p-NF-κB p65/NF-κB p65 and FoxO1 were increased(P<0.01). In the hippocampus and serum, the levels of IL-1ß, IL-6, TNF-α, and MDA were increased(P<0.01), and the activity of SOD and the levels of GSH, DA, 5-HT, NE, and BDNF were reduced(P<0.01). The treatment with high-dose Jiaotai Pills increased the sucrose preference rate, movement distance, and the number of crossing centers(P<0.05), reduced tail suspension time and swimming immobility time(P<0.01), elevated hippocampal SIRT1 expression level(P<0.01), decreased hippocampal and serum IL-1ß, IL-6, TNF-α, and MDA levels(P<0.01), potentiated SOD activity, and up-regulated GSH, DA, 5-HT, NE, and BDNF levels in the hippocampus and serum(P<0.05, P<0.01) in model mice. In conclusion, the results showed that Jiaotai Pills could improve the depression behaviors of model mice with CUMS-induced depression, and the underlying mechanism was related to the up-regulation of SIRT1 in the hippocampus of mice to exert anti-inflammatory and anti-oxidative stress effects.


Assuntos
Antidepressivos , Depressão , Animais , Comportamento Animal , Cromatografia Líquida , Depressão/tratamento farmacológico , Depressão/etiologia , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas , Hipocampo , Camundongos , Simulação de Acoplamento Molecular , Sirtuína 1/genética , Estresse Psicológico , Espectrometria de Massas em Tandem
16.
Inorg Chem ; 59(15): 10996-11008, 2020 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-32686404

RESUMO

Electron-donating N-heterocyclic carbenes (Lewis bases, LB) and electron-accepting Lewis acids (LA) have been used in tandem to yield donor-acceptor complexes of inorganic tetrelenes LB·EH2·LA (E = Si, Ge, and Sn). Herein, we introduce the new germanium (II) dihydride adducts ImMe2·GeH2·BH3 (ImMe2 = (HCNMe)2C:) and ImiPr2Me2·GeH2·BH3 (ImiPr2Me2 = (MeCNiPr)2C:), with the former complex containing nearly 40 wt % germanium. The thermal release of bulk germanium from ImMe2·GeH2·BH3 (and its deuterated isotopologue ImMe2·GeD2·BD3) was examined in solution, and a combined kinetic and computational investigation was undertaken to probe the mechanism by which Ge is liberated. Moreover, the thermolysis of ImMe2·GeH2·BH3 in solution cleanly affords conformal nanodimensional layers of germanium as thin films of variable thicknesses (20-70 nm) on silicon wafers. We also conducted a computational investigation into potential decomposition pathways for the germanium(II)- and tin(II)-dihydride complexes NHC·EH2·BH3 (NHC = [(HCNR)2C:]; R = 2,6-iPr2C6H3 (Dipp), Me, and H; and E = Ge and Sn). Overall, this study introduces a mild and convenient solution-only protocol for the deposition of thin films of Ge, a widely used semiconductor in materials research and industry.

17.
Biomed Chromatogr ; 33(9): e4542, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30947404

RESUMO

A highly selective and efficient LC-MS/MS method was developed to determine the plasma concentration of magnolol, hesperidin, neohesperidin and geniposide following oral administration of Zhi-Zi-Hou-Po decoction in normal and depressed rats. Plasma samples were pretreated by protein precipitation with methanol. Chromatographic separation was performed on an XTerra® MS C18 column using a gradient elution with a mobile phase composed of acetonitrile-0.1% aqueous formic acid. The proposed method was validated to be specific, accurate and precise for the analytes determination in plasma samples. The calibration curves displayed good linearity over definite concentration ranges for the analytes. The intra- and inter-day precision of the proposed method at three different levels were all within <11.13% and the relative errors ranged from -8.46 to 8.93%. The recovery of the four compounds ranged from 82.72 to 89.08% and no apparent matrix effect was observed during sample analysis. After full validation, the established method was successfully applied for comparing the pharmacokinetics of four components between normal and depressed rats. The results showed that the AUC and Cmax of four analytes in depressed rats were significantly different from those in normal rats and might provide helpful information to guide the clinical use of Zhi-Zi-Hou-Po to treat depression.


Assuntos
Depressão , Medicamentos de Ervas Chinesas/farmacocinética , Iridoides/farmacocinética , Administração Oral , Animais , Compostos de Bifenilo/sangue , Compostos de Bifenilo/química , Compostos de Bifenilo/farmacocinética , Corticosterona/efeitos adversos , Depressão/induzido quimicamente , Depressão/metabolismo , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/administração & dosagem , Hesperidina/sangue , Hesperidina/farmacocinética , Iridoides/administração & dosagem , Iridoides/sangue , Iridoides/química , Lignanas/sangue , Lignanas/química , Lignanas/farmacocinética , Limite de Detecção , Modelos Lineares , Masculino , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes
18.
Neural Plast ; 2019: 1571392, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31814820

RESUMO

Evidence suggests that inflammation and neurogenesis play an important role in major depressive disorder (MDD). Mahuang-Fuzi-Xixin decoction (MFX), as the traditional Chinese prescription, has been widely applied for asthma, migraine, and MDD in clinics. However, the effects of MFX on the potential mechanism in MDD are still unclear. Hence, the present study is aimed at exploring whether the antidepressive effect of MFX is connected to the anti-inflammatory and promoting neurogenesis. Besides, lipopolysaccharide (LPS) of Gram-negative bacteria can induce depressive-like behaviors. We demonstrated that administration of MFX corrected the depressive-like behaviors in LPS-induced mice and significantly decreased the expression of IL-1ß in the hippocampus. LPS injection induced a significant increase in the levels of NLRP3, cleaved caspase-1 p20, and ASC in the hippocampus, as well as Trx-interacting protein (TXNIP), and MFX could reverse this change. What is more, treatment of MFX increased the level of doublecortin (DCX), brain-derived neurotrophic factor (BDNF), and tropomyosin-related kinase receptor B (TrkB) in the hippocampus which means that MFX could promote the neurogenesis. In conclusion, the study indicates that MFX relieves a depressive-like state in LPS-induced mice through the inhibition of the NLRP3 inflammasome and the enhancement of the neurogenesis pathway.


Assuntos
Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Inflamassomos/efeitos dos fármacos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Neurogênese/efeitos dos fármacos , Animais , Antidepressivos/farmacologia , Comportamento Animal/efeitos dos fármacos , Depressão/metabolismo , Modelos Animais de Doenças , Proteína Duplacortina , Medicamentos de Ervas Chinesas/farmacologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Inflamassomos/metabolismo , Inflamação/induzido quimicamente , Inflamação/metabolismo , Interleucina-1beta/metabolismo , Lipopolissacarídeos , Camundongos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo
19.
Biomed Chromatogr ; 32(11): e4329, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29972688

RESUMO

Acute hepatitis is a severe inflammatory disease with high mortality rates. Dehydrocavidine (DC), berberine (BB) and palmatine (PT), the bioactive components of Yanhuanglian total alkaloids extract (YTAE), may play important roles in its protective effect against acute hepatitis. The present study was designed to compare the pharmacokinetic properties of DC, BB and PT after oral administration of YTAE in normal and acute hepatitis rats. The plasma pharmacokinetic profiles of three major bioactive alkaloids from YTAE were analyzed using an LC-MS/MS method. It was found that the pharmacokinetic parameters of DC, BB and PT represented a statistically significant difference (p ˂ 0.05) between the normal rats and the acute hepatitis rats after administration of YTAE. The results indicated that the Cmax , T1/2ß and AUC of DC, BB and PT in acute hepatitis rats were significantly increased, whereas the CL and Vd values were remarkably decreased (p ˂ 0.05) over those of the normal rats. The results suggested that the pharmacokinetic behavior of the active constituents from YTAE could be changed when it was used in acute hepatitis animals, which provide a meaningful basis for developing a clinical dosage regimen in the treatment of acute hepatitis by YTAE.


Assuntos
Alcaloides/farmacocinética , Medicamentos de Ervas Chinesas/farmacocinética , Hepatite/metabolismo , Doença Aguda , Administração Oral , Alcaloides/administração & dosagem , Alcaloides/sangue , Animais , Medicamentos de Ervas Chinesas/administração & dosagem , Modelos Lineares , Masculino , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
20.
Beilstein J Org Chem ; 14: 869-874, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29765467

RESUMO

Two novel D-A bipolar blue phosphorescent host materials based on phenothiazine-5,5-dioxide: 3-(9H-carbazol-9-yl)-10-ethyl-10H-phenothiazine-5,5-dioxide (CEPDO) and 10-butyl-3-(9H-carbazol-9-yl)-10H-phenothiazine-5,5-dioxide (CBPDO) were synthesized and characterized. The photophysical, electrochemical and thermal properties were systematically investigated. CEPDO and CBPDO not only have a high triplet energy but also show a bipolar behavior. Moreover, their fluorescence emission peaks are in the blue fluorescence region at 408 nm and the fluorescence quantum efficiency (Φ) of CEPDO and CBPDO were 62.5% and 59.7%, respectively. Both CEPDO and CBPDO showed very high thermal stability with decomposition temperatures (Td) of 409 and 396 °C as well as suitable HOMO and LUMO energy levels. This preferable performance suggests that CEPDO and CBPDO are alternative bipolar host materials for the PhOLEDs.

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